Responding imprinted genes. This was done using the statistical language R [16].Functional Enrichment AnalysisFor analyzing significantly enriched functional categories, we used the functional annotation tool available in the Database for Annotation, Visualization and Integrated Discovery (DAVID) [10]. We determined which GO categories are statistically overrepresented in different sets of genes. Enrichment was evaluated through the Fisher Exact test using a significance level or p-value threshold of 0.05. We suspected that some functional categories with a high statistical significance may show overrepresentation even when annotated only to a single gene. In that case, it would not be clear if this function is related to monoallelic expression of the gene in certain tissues, or when it is biallelically expressed in other tissues. Therefore we required that each GO term considered here is annotated to at least two human (mouse) genes. For the most specific GO terms, we ran the same enrichment analysis procedures by using the biological process GO_FAT database instead of using the general GO knowledgebase. GO_FAT is a subset of the full set of GO terms that was established by the DAVID team so that the broadest terms should not overshadow more specific terms. The smaller the p-value, the more enriched is the Ezatiostat corresponding GO term in the group of imprinted genes with respect to all human or mouse genes. TheResultsIn this study we addressed the question whether imprinted genes as a group fulfill specific functions in mammalian organisms. For this, we tested if specific GO terms are overrepresented in the group of imprinted genes in comparison to all genes in the human or mouse TLK199 genome. Of the 41 selected human imprinted genes, 38 are annotated in the GO database that contains in total 14116 human genes. In contrast, all 48 mouse imprinted genes are among the 14219 annotated mouse genes. One should note, though, that many genes are represented by more than one transcript in the GO database.Cellular Functions of Genetically Imprinted GenesImprinted genes are involved in developmental, transport and regulatory functionsFirst, we analyzed which terms of the Gene Ontology are enriched in the full set of all imprinted genes when compared to the set of all human genes or all mouse genes. We concentrate in this analysis on GO terms that are shared by at least 2 different imprinted genes. In this way, we assume to emphasize those cellular functions that relate to the controlled mono-allelic expression of the set of genes studied here. The terms of the GO database are organized in a tree-like structure where a few general terms such as developmental process are linked to numerous more specific terms on the next hierarchical level. Terms that showed an overrepresentation of imprinted genes in both human and mouse with p-values below 0.05 are listed in supplemental tables S2 and S3. In the human, the term system development is the term with the lowest p-value. This term is associated with 15 out of the 38 human imprinted genes. This corresponds to a 2.6 fold enrichment in comparison to the annotation frequency in the group of all genes. Cellular processes is the term which is associated with the largest number of imprinted genes in the human: 32 imprinted genes (84.2 of all imprinted genes) are associated with this term, whereas this is only the case for 74.6 12926553 of all genes. For comparison, the imprinted genes in mouse showed a narrower range of 1.8 an.Responding imprinted genes. This was done using the statistical language R [16].Functional Enrichment AnalysisFor analyzing significantly enriched functional categories, we used the functional annotation tool available in the Database for Annotation, Visualization and Integrated Discovery (DAVID) [10]. We determined which GO categories are statistically overrepresented in different sets of genes. Enrichment was evaluated through the Fisher Exact test using a significance level or p-value threshold of 0.05. We suspected that some functional categories with a high statistical significance may show overrepresentation even when annotated only to a single gene. In that case, it would not be clear if this function is related to monoallelic expression of the gene in certain tissues, or when it is biallelically expressed in other tissues. Therefore we required that each GO term considered here is annotated to at least two human (mouse) genes. For the most specific GO terms, we ran the same enrichment analysis procedures by using the biological process GO_FAT database instead of using the general GO knowledgebase. GO_FAT is a subset of the full set of GO terms that was established by the DAVID team so that the broadest terms should not overshadow more specific terms. The smaller the p-value, the more enriched is the corresponding GO term in the group of imprinted genes with respect to all human or mouse genes. TheResultsIn this study we addressed the question whether imprinted genes as a group fulfill specific functions in mammalian organisms. For this, we tested if specific GO terms are overrepresented in the group of imprinted genes in comparison to all genes in the human or mouse genome. Of the 41 selected human imprinted genes, 38 are annotated in the GO database that contains in total 14116 human genes. In contrast, all 48 mouse imprinted genes are among the 14219 annotated mouse genes. One should note, though, that many genes are represented by more than one transcript in the GO database.Cellular Functions of Genetically Imprinted GenesImprinted genes are involved in developmental, transport and regulatory functionsFirst, we analyzed which terms of the Gene Ontology are enriched in the full set of all imprinted genes when compared to the set of all human genes or all mouse genes. We concentrate in this analysis on GO terms that are shared by at least 2 different imprinted genes. In this way, we assume to emphasize those cellular functions that relate to the controlled mono-allelic expression of the set of genes studied here. The terms of the GO database are organized in a tree-like structure where a few general terms such as developmental process are linked to numerous more specific terms on the next hierarchical level. Terms that showed an overrepresentation of imprinted genes in both human and mouse with p-values below 0.05 are listed in supplemental tables S2 and S3. In the human, the term system development is the term with the lowest p-value. This term is associated with 15 out of the 38 human imprinted genes. This corresponds to a 2.6 fold enrichment in comparison to the annotation frequency in the group of all genes. Cellular processes is the term which is associated with the largest number of imprinted genes in the human: 32 imprinted genes (84.2 of all imprinted genes) are associated with this term, whereas this is only the case for 74.6 12926553 of all genes. For comparison, the imprinted genes in mouse showed a narrower range of 1.8 an.